Progression-free Time Research Articles

Responses to Targeted Therapy among Organs Affected by Metastasis in Patients with Renal Cell Carcinoma are Organ-Specific.

Previous reports showed that targeted therapy efficacy varied due to different metastatic organs in patients with metastatic renal cell carcinoma (mRCC). This study aimed to further evaluate the response and progression-free time (PFT) of individual metastatic organs. Data from mRCC patients, who were treated with sunitinib between January 2008 to December 2018, were retrospectively reviewed. Individual metastatic organs were assessed separately by The Response Evaluation Criteria in Solid Tumors criteria. We evaluated response heterogeneity and PFT as characteristics of 281 individual organs affected by mRCC in 213 patients. The objective response rates in these organs were 72.7% in pancreas, 63.7% in spleen, 14.3% in adrenal glands, 13.5% in bone and soft tissue, 11.6% in lymph nodes, 11.6% in lungs, and 9.1% in liver. The median PFT was 15.2 months (95% confidence interval [CI] 2.7-27.7 months) for adrenal glands, 13.2 months (95% CI 3.5-22.9 months) for bone and soft tissue, 9.0 months (95% CI 7.6-10.4 months) for lymph nodes, 8.6 months (95% CI 6.3-10.9 months) for lungs, and 5.2 months (95% CI 2.9-7.5 months) for liver. Median PFT was not reached in pancreas and spleen, but was > 22.8 months and > 20.6 months, respectively. Our results indicated that organs affected by metastasis may have individual responses to sunitinib treatment. The pancreas and spleen may have the best responses, and liver may have the worst response. Further research is needed to verify these findings.

Criteria for Responses of Renal Cancer Metastases to Targeted and Immunotherapy

Objective : to compare the criteria for tumor response to targeted therapy and immunotherapy for metastatic kidney cancer. Subjects and methods. The paper presents the results of diagnosis and treatment in 20 patients with metastatic renal cell carcinoma. Of these, 10 patients took interferon- α as immunotherapy, 10 patients received sorafenib as targeted therapy. The response of targeted foci was assessed using computed tomography according to the RECIST 1.1, Choi, mChoi, and SACT criteria. Control CTs were performed every 3 months until the disease progressed. The progression-free time was calculated using the Kaplan-Meier method. Results. The investigation revealed the coincidence according to the RECIST 1.1, Choi, mChoi and SACT criteria in terms of progression in all assessed cases; that according to the partial response criterion in 50% of cases, and that according to the stability criterion in 8.7%. Other cases displayed a discrepancy in the interpretation of the results. The progression-free time for patients receiving immunotherapy according to the RECIST 1.1 criteria, the Choi and mChoi criteria, and the SACT criteria was 6.3 ± 0.7, 4.3 ± 0.6, and 4.5 ± 0.7 months, respectively. The progression-free time for patients receiving targeted therapy according to the above criteria was 10.3 ± 1.2, 6.4 ± 1.2, and 6.7 ± 1.3 months. Conclusion. Tumor response to therapy is critical in evaluating the efficiency of anticancer treatment. Targeted and immunological drugs cause not only a tumor size change, but also necrosis and cystic degeneration. The criteria based not only on changes in size, but also on those in the density of tumor foci have a shorter progression-free time and make it possible to identify patients with disease progression at an earlier date.

1203P Prognostic implication of clinical decision support system (CDSS) for colorectal cancer

Oncologists are challenged to personalize care with rapidly changing scientific evidence treatment guidelines and drug availability. IBM Watson for Oncology (WFO) is a cognitive computing clinical decision support systems (CDSS) that provides oncologists with evidence-based treatment recommendation for a variety of cancer treatment. WFO has been proven to be useful for decision-making in breast and lung cancers, but to date, research on colorectal cancer is limited. In the present study, we compared concordance of WFO with multidisciplinary tumor board from Daegu Catholic University Medical Center (DCUMC) and investigated the impact on patient prognosis We enrolled 200 patients with colorectal cancer, all treated between 2016 and 2018. Cases were processed using WFO, and the output was compared to blinded tumor board recommendations. Concordance was achieved when the DCUMC suggestion was in the “Recommended” or “For consideration” categories given by WFO. A total 200 cases were assessed, 129 (64.5%) were colon cancer and 71 (35.5%) were rectal cancer. The overall concordance rate was 74%; 71.3% for colon cancer, 78.9% for rectal cancer. Among all patients, the progression free time (PFS) was significantly better in concordant patients than in nonconcordant patients. (36m vs 20m, p=0.001) Treatment recommendations made by the DCUMC and WFO were highly concordant in colorectal cancer patients. Survival was better in concordant patients than in nonconcordant patients.

Abstract 3267: Identification of a novel biomarker response in a prospective clinical trial of immune checkpoint blockade in recurrent ovarian carcinoma

Abstract The role of immune checkpoint inhibitors (ICPIs) in ovarian cancer continues to be refined. The presence of intratumoral T cells in ovarian tumors correlates with improved survival and progression, suggesting that immune modulation, such as by ICPIs, may be beneficial. However, a better understanding of the immune effects following ICPI use, particularly in those with a long progression free survival, is needed. Thus, we used imaging mass cytometry (IMC) to compare the tumor immune landscape of patients with ovarian cancer before and after a CTLA4 immune checkpoint inhibitor treatment to determine the association between alterations in immune landscapes and progression free survival. Fine needle biopsies were obtained from 8 patients with recurrent platinum-resistant ovarian carcinoma enrolled in a phase 2 randomized trial evaluating the efficacy of Tremelimumab and Durvalumab (CTLA4 and PDL1 checkpoint inhibitors, respectively) in recurrent ovarian cancer treatment. Each patient had a pre-treatment biopsy and on-treatment biopsy after 3 cycles of CTLA4 inhibitor therapy. Progression free time (PFS) was recorded with 3 patients with a long PFS (>180 days) and 5 with short PFS (<60 days). Formalin fixed paraffin embedded (FFPE) tissue sections were stained for IMC analysis via Fluidigm protocol with 34 metal-tagged antibodies to detect various cell and immune related markers. The IMC data was obtained using the Fluidigm Helios CyTOF instrument and Hyperion Imaging System laser ablation module. A novel image informatics pipeline through Matlab was used to assess the image intensity of each marker and cell location. Using the developed image informatics pipeline, cell types and locations were analyzed for 16 samples from 8 patients. In all patients, mean CD8+ T cell densities had an increased trend in on-treatment vs pre-treatment samples (205.6 v 129.9 cells/mm2, p=0.086). An analysis of cell location found that in all patients on-treatment, the mean number of CD8+ T cells adjacent to M2 macrophages increased significantly (0.09 v. 0.17 cells, p = 0.0460) as well as the mean number of CD8+ T cells adjacent to B7H4+ tumor cells (0.035 v. 0.01 cells, p = 0.046). Furthermore, patients with a long PFS had a significantly higher number of CD8+ cells neighboring B cells on-treatment than short PFS (0.12 v. 0.27 cells, p=0.028). Using IMC and novel image informatics pipeline, we found that patients with recurrent ovarian cancer treated with Tremelimumab with a long PFS mounted a significant immune response compared to patients with a short PFS, with a higher number of CD8+ T cells neighboring B cells after treatment. For all patients, the immune landscape altered after treatment. To our knowledge, this is the first known use of IMC to demonstrate immune response in ovarian cancer following ICPI therapy. Overall, IMC and image informatics pipeline are robust tools that simultaneously analyze multiple biomarkers and spatial location of cells to better assess the tumor immune microenvironment and cellular interactions. Citation Format: Han Cun, Emily M. Hinchcliff, Ying Zhu, Sammy Ferri-Borgogno, Rita Cheng, Jared K. Burks, Stephen T. Wong, Amir A. Jazaeri, Samuel C. Mok. Identification of a novel biomarker response in a prospective clinical trial of immune checkpoint blockade in recurrent ovarian carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3267.

Analysis of the clinical effect of osimertinib on 90 cases with advanced lung adenocarcinoma.

BackgroundPrimary or secondary drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) is a new challenge in the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR-TKI, and its efficacy and safety in NSCLC patients with first-generation EGFR-TKI resistance, especially lung adenocarcinoma, are not yet clear. The purpose of this study was to observe the efficacy and adverse reactions of osimertinib in the treatment of patients with advanced lung adenocarcinoma.MethodsFrom January 2017 to December 2018, 90 patients with advanced (stage IV) lung adenocarcinoma were diagnosed in Shanghai Chest Hospital. The disease of these patients (94.4%) progressed after first-line EGFR-TKI treatment, and 43.3% of patients received third-line or beyond third-line treatment. The efficacy and adverse reactions of osimertinib treatment were observed.ResultsAmong 90 patients with advanced lung adenocarcinoma, 57 (63.3%) achieved partial response (PR), 27 (30.0%) had stable disease (SD), and 6 (6.7%) had progressive disease (PD). The objective response rate (ORR) was 63.3%, and the disease control rate (DCR) was 93.3%. The median progression-free time (mPFS) was 10.41 months (95% CI: 8.91–11.91 months), and the median overall survival (mOS) was 31.37 months (95% CI: 26.37–36.37 months). The incidence of adverse events of degree 3 and above was 7.78%. The main adverse events were diarrhea (28.9%) and rash (24.4%). After symptomatic treatment, the incidence of adverse events was significantly reduced.ConclusionsOsimertinib has a definite curative effect in the treatment of patients with advanced lung adenocarcinoma, and the incidence of adverse reactions is low.

Selumetynib — pierwszy lek skuteczny w terapii nerwiakowłókniaków splotowatych w przebiegu neurofibromatozy typu 1

Plexiform neurofibromas progress and increase their size throughout the patient’s life, causing body deformity, disability, and higher mortality. Complete tumour resection is often dificult due to the large size of the plexiform neurofibroma and nerve infiltration. Treatment with MEK inhibitors appears to be a promising therapeutic option that allows reducing the mass of tumours. In the clinical trial NCT01362803 on the effect of selumetinib on inoperable plexiform neurofibromas in type 1 neurofibromatosis, children aged 3 to 18 years were involved. 74% of patients showed a partial response, defined as a reduction of at least 20% in tumour volume. Progression-free time was on average 3 years. The best results were observed after the 16th cycle of therapy. In addition to reducing tumour volume, a significant clinical reduction in pain intensity has also been demonstrated, which has resulted in an improvement in overall quality of life and daily functioning. At the same time, 78% of children from the control sample showed an increase of at least 20% in neurofibroma size. The results of studies on the effects of selumetinib in the adult population are also promising. Selumetinib treatment was well tolerated in both age groups. Gastrointestinal and skin complaints were most commonly observed. Most symptoms could be alleviated by appropriate treatment. More serious but rarer complications were cardiomyopathy and ophthalmic complications.

Single course of intravesical Bacillus Calmette-Guerin versus single course with maintenance therapy in the management of nonmuscle invasive bladder cancer: A prospective randomized study.

Objective:The objective of the study was to compare maintenance versus single course of intravesical Bacillus Calmette–Guerin (BCG) in the management of high-risk nonmuscle invasive bladder cancer (NMIBC) regarding recurrence, progression, survival, and complications.Patients and Methods:After transurethral resection of bladder tumor (TURBT), Group I patients (33) received weekly doses of 90 mg of live attenuated Pasteur strain of BCG. The course was started 14 days after the second TURBT for 6 consecutive weeks. In Group II: 35 patients, the induction schedule was followed by 3 weekly instillations at months 3, 6, and 12 as a maintenance course. Recurrence, progression rates, survival, and toxicity were assessed in both the groups.Results:Patients with induction therapy alone had significantly higher recurrence rate than those received maintenance therapy (55.6% vs. 19.2%, P = 0.01). The 5-year recurrence-free survival rate was 41% and 78% in both the groups, respectively. There was no significant difference regarding the progression rate for both the groups. The mean 5-year progression-free time was comparable between the two groups. The 5-year progression-free survival was 69.8% for patients who underwent induction therapy alone compared to 70.7% for maintenance therapy. Overall local adverse events were significantly higher in patients who underwent maintenance treatment protocol.Statistical Analysis Used:SPSS package version 20 and Kaplan–Meier curves were used to evaluate the survival rate.Conclusions:Maintenance doses of BCG significantly decrease and delay the recurrence of high-risk NMIBC. However, there is no significant favor as regards tumor progression. Maintenance doses of BCG are significantly associated with a higher incidence of local adverse effects than induction doses alone.

394O - Health-related quality of life (HRQoL) evaluation in the REGOMA trial: A randomized, phase II clinical trial analyzing regorafenib activity in relapsed glioblastoma patients

BackgroundREGOMA trial showed that regorafenib (REG) significantly improved OS and PFS in patients (pts) with relapsed GBM with respect to lomustine (LOM). REG showed a different toxicity profile compared to LOM. Here, we report final results of the HRQoL assessment, a secondary end point. MethodsHRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20) administered before any MRI assessments, every 8 weeks (+/- 2 weeks) until disease progression. To evaluate treatment impact on HRQoL, questionnaires at progression were excluded. Mixed-effect linear models were fitted for each of the HRQOL domain to examine the change over progression-free time within and between arms. The models included the time of questionnaire assessment, the treatment group and their interaction, as fixed effects, and a compound symmetry covariance structure for the random effects. Differences of at least 10 points were classified as a clinically meaningful change. To correct for multiple comparisons and to avoid type I error, the level of significance was set at P=0.01 (2-sided). ResultsOf 119 randomized pts, 117 participated in the HRQoL evaluation, and 114 had a baseline assessment (n=56 REG; n=58 LOM).No statistically significant differences were observed in any generic or cancer specific domain during treatment in the REG and LOM arms, or between the two arms, except for the appetite loss scale which was significantly worse in PTS treated with REG (Global mean 14.7 (SD=28.6) vs 7.6 (SD=16.0); p=0.0081). The rate of pts with a clinically meaningful worsening for appetite loss was not statistically different between the two arms (9 out of 24 and 0 out of 13 in the REG and LOM arm, respectively; p=0.02). ConclusionsIn the REGOMA trial, HRQoL did not change during regorafenib treatment. Pts treated with regorafenib and lomustine reported no significant difference in HRQoL. Legal entity responsible for the studyGiuseppe Lombardi. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Cost-effectiveness of pembrolizumab as first-line treatment of locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based therapy in the United States.

93 Background: Pembrolizumab is indicated as first-line therapy for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (mUC) whose tumors express PD-L1 with a combined positive score (CPS) ≥ 10. This study aims to evaluate the cost‐effectiveness of pembrolizumab versus carboplatin plus gemcitabine in this setting from the US payer perspective. Methods: A partitioned-survival model was developed to measure the costs and effectiveness over a 20-year time horizon with an annual discount of 3%. Clinical outcomes of overall survival (OS) and progression-free survival, safety outcomes and time on treatment were modeled using data from the KEYNOTE-052 clinical trial for pembrolizumab and four clinical trials for carboplatin plus gemcitabine. Because clinical trials directly comparing these treatment strategies are not available, a simulation treatment comparison and a network meta-analysis were conducted to estimate comparative efficacy. Quality of life data extracted from EQ-5D questionnaires administered in KEYNOTE-052 were used to estimate utility, while cost data were estimated using US pricing lists and real-world data. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Pembrolizumab was also compared with gemcitabine monotherapy in the scenario analyses. Results: Pembrolizumab was associated with a survival gain of 2.47 years and 1.90 quality adjusted life years (QALY), an incremental cost of $155,238, and an incremental cost per QALY gained of $81,493 versus carboplatin plus gemcitabine. Results were most sensitive to the time horizon, discount rate, pembrolizumab dosing intensity and OS hazard ratio. Pembrolizumab had 87% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears cost-effective versus carboplatin plus gemcitabine as first-line treatment of cisplatin-ineligible and PD-L1 positive mUC patients in the US. The comparison of pembrolizumab with gemcitabine monotherapy yields similar conclusions.

OS7.3 Health-related quality of life (HRQoL) evaluation in the REGOMA trial: a randomized, phase II clinical trial analyzing regorafenib activity in relapsed glioblastoma patients

Abstract BACKGROUND REGOMA trial showed that regorafenib (REG) significantly improved OS and PFS in patients (pts) with relapsed GBM with respect to lomustine (LOM). REG showed a different toxicity profile compared to LOM. Here, we report final results of the HRQoL assessment, a secondary end point. MATERIAL AND METHODS HRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20) administered before any MRI assessments, every 8 weeks (+/- 2 weeks) until disease progression. To evaluate treatment impact on HRQoL, questionnaires at progression were excluded. Mixed-effect linear models were fitted for each of the HRQOL domain to examine the change over progression-free time within and between arms. The models included the time of questionnaire assessment, the treatment group and their interaction, as fixed effects, and a compound symmetry covariance structure for the random effects. Differences of at least 10 points were classified as a clinically meaningful change. To correct for multiple comparisons and to avoid type I error, the level of significance was set at P=0.01 (2-sided). RESULTS Of 119 randomized pts, 117 partecipated in the HRQoL evaluation, and 114 had a baseline assessment (n=56 REG; n=58 LOM). No statistically significant differences were observed in any generic or cancer specific domain during treatment in the REG and LOM arms, or between the two arms, except for the appetite loss scale which was significantly worse in PTS treated with REG (Global mean 14.7 (SD=28.6) vs 7.6 (SD=16.0); p=0.0081). The rate of pts with a clinically meaningful worsening for appetite loss was not statistically different between the two arms (9 out of 24 and 0 out of 13 in the REG and LOM arm, respectively;p=0.02). CONCLUSION In the REGOMA trial, HRQoL did not change during regorafenib treatment. Pts treated with regorafenib and lomustine reported no significant difference in HRQoL.

Efficacy and Dosimetry Prognostic Factors of Ultrosound/CT-Guided 125I Seed Implantation for Locally Recurrent Soft Tissue Sarcoma

To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1∼144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI (> 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 (> 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

Tratamento Quimioterápico do Mesotelioma Pleural Maligno: Revisão Sistemática

Introdução: O mesotelioma pleural maligno é um câncer raro, agressivo e que apresenta expectativa de aumento na incidência até 2030. As melhores formas de tratar essa neoplasia continuam em debate. Objetivo: Sintetizar as evidências de eficácia e segurança dos esquemas quimioterápicos de primeira linha disponíveis para o tratamento do mesotelioma pleural maligno. Método: Foram utilizadas as bases bibliográficas LILACS, MEDLINE, Scopus, Cochrane Controlled Trials Register e Web of Science. Buscaram-se estudos na literatura cinzenta. Os critérios de elegibilidade incluíram ensaios randomizados de fases II ou III, de pacientes com mesotelioma pleural virgem de tratamento quimioterápico, submetidos a qualquer regime terapêutico, tendo como controle outros esquemas quimioterápicos ou controle ativo de sintomas, e apresentando tempo de sobrevida global, tempo livre de progressão, resposta tumoral e toxicidade como desfechos. Todas as etapas foram realizadas por dois revisores, de forma independente. O protocolo da revisão foi registrado no International Prospective Register of Systematic Reviews (PROSPERO 2014: CRD42014014388). Resultados: Treze estudos envolvendo 14 esquemas terapêuticos foram incluídos. O único esquema quimioterápico que se apresentou superior ao comparado com significância estatística nos três desfechos de eficácia foi cisplatina + pemetrexede. Cisplatina + pemetrexede e cisplatina + gemcitabina apresentaram mais casos de toxicidade graus 3 e 4. Conclusão: Existem boas evidências para recomendar combinações de derivado de platina e antifolato como opção de primeira escolha no tratamento quimioterápico do mesotelioma pleural. Mais estudos clínicos são necessários para embasar decisões de incorporação dos antifolatos no tratamento rotineiro dessa neoplasia no Brasil.

Health-related quality of life (HRQoL) evaluation in the REGOMA trial: A randomized, phase II clinical trial analyzing regorafenib activity in relapsed glioblastoma patients.

2045 Background: REGOMA trial showed that regorafenib (REG) significantly improved OS and PFS in relapsed glioblastoma (GBM) patients (pts) with respect to lomustine (LOM). REG showed a different toxicity profile compared to LOM. Here, we report final results of the HRQoL assessment, a secondary end point. Methods: HRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20) administered before any MRI assessments, every 8 weeks (+/- 2 weeks) until disease progression. To evaluate treatment impact on HRQoL, questionnaires at progression were excluded. Mixed-effect linear models were fitted for each of the HRQOL domain to examine the change over progression-free time within and between arms. The models included the time of questionnaire assessment, the treatment group and their interaction, as fixed effects, and a compound symmetry covariance structure for the random effects. Differences of at least 10 points were classified as a clinically meaningful change. To correct for multiple comparisons and to avoid type I error, the level of significance was set at P = 0.01 (2-sided). Results: Of 119 randomized pts, 117 participated in the HRQoL evaluation, and 114 had a baseline assessment (n = 56 REG; n = 58 LOM). No statistically significant differences were observed in any generic or cancer specific domain during treatment in the REG and LOM arms, or between the two arms, except for the appetite loss scale which was significantly worse in PTS treated with REG (Global mean 14.7 (SD = 28.6) vs 7.6 (SD = 16.0); p = 0.0081). The proportion of pts with a clinically meaningful worsening for appetite loss was not statistically different between the two arms (9 out of 24 and 0 out of 13 in the REG and LOM arm, respectively; p = 0.0146). Conclusions: In the REGOMA trial, HRQoL did not change during REG treatment. Pts treated with REG and LOM reported no significant difference in HRQoL. Clinical trial information: NCT02926222. [Table: see text]

Impact of BRCA mutation status and time to platinum resistance on patients with advanced ovarian cancer.

5561 Background: The influence of germline BRCA1/2 mutations (gBRCAmt) on ovarian cancer patients (pts) long-term survival remains controversial. Methods: 228 pts with serous and endometrial ovarian cancer stage Ic-IV were enrolled in the retrospective study. Next-generation sequencing testing of BRCA1/2 in blood was employed. Progression-free survival (PFS), overall survival (OS) and time to platinum resistance (TPR) were analyzed. TPR was defined as time from first line chemotherapy to registration of platinum resistance relapse. Results: The rate of pathogenic gBRCAmt was defined in 29.4% (67/228) pts. There was no any significant difference between BRCA1/2 mutation carries and non-carries in both PFS (18.3 and 16.7 months, p = 0.27, HR 0.79, 95%CI 0.52-1.20) and OS (71.9 and 79.1 months, p = 0.69, HR 0.88, 95%CI 0.46-1.68). However, TPR was significantly longer in pts with gBRCAmt than in germline BRCA wild type (gBRCAwt) pts (51.4 and 34.4 months, p = 0.05, HR 0.60, 95% CI 0.36-0.98). Pts with gBRCAmt had poor prognosis after registration of platinum resistance. gBRCAwt pts had longer survival than gBRCAmt after platinum-resistance relapse: 33.7 and 16.9 months respectively (p = 0.05; HR 1.85, 95%CI 1.02-4.08). Conclusions: Our finding provided possible explanation of equal survival of pts with or without BRCA1/2 mutations. Long-term sensitivity to platinum-based chemotherapy allowed pts with gBRCA1/2mt to control the disease for a long period of time. However the non-platinum regimens had less efficacy in pts with gBRCAmt than gBRCAwt after platinum resistance.

Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

Abstract P4-08-19: Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype

Abstract Background: Overall survival (OS) is the established endpoint to evaluate the effects of drug treatment in comparative clinical trials of metastatic breast cancer. But assessing OS requires long follow-up periods and large sample size, which raise costs and create long delays in the drug approval process. Progression-free survival (PFS) or time to progression (TTP) is considered as a surrogate for OS and is often used as an alternative to OS. In some cancers the two endpoints are highly correlated, but in others they are not. Furthermore, the effect of breast cancer (BC) subtypes on the surrogacy of PFS/TTP for OS has not been completely defined. Method: A systematic literature review of randomized control trials was conducted to identify studies that reported both the hazard ratio (HR) of PFS/TTP and OS for BC subtypes {i.e. estrogen receptor (ER) positive, HER2 positive, and triple negative (TN)}. The correlation between the HR of PFS/TTP and OS was evaluated using weighted Spearman's rank correlation. Results: A total of 49 trials (34 phase III trials and 15 phase II trials) were selected for analysis. Among these trials, there were 8 comparison trials between one chemotherapy and another chemotherapy regimen, 18 comparison trials between chemotherapy and chemotherapy plus molecularly-targeted therapy, 9 comparison trials between one endocrine therapy and another endocrine therapy, and 5 comparison trials between endocrine therapy and endocrine therapy plus molecularly-targeted therapy. There were 17 trials reporting the HR of PFS/TTP and OS for ER positive, 16 trials for HER2 positive, and 9 trials for TN BC. Weighted Spearman's rank correlation revealed that coefficient between the HR of PFS/TTP and OS was 0.721(p<.0001) for all trials, 0.873(p< .0001) for ER positive, 0.642(p=0.0055) for HER2 positive, and 0.615(p=0.078)for TN BC. Conclusion: There was a strong correlation between the HR of PFS/TTP and OS for ER positive BC, and a weak correlation between the HR of PFS/TTP and OS for HER2 positive and TN BC. The validity of using PFS/TTP as an OS surrogate marker was shown for metastatic BC, especially for ER positive BC. Citation Format: Tsukioki T, Taira N, Sakamaki K, Suzuki Y, Kajiwara Y, Hatono M, Takahashi Y, Kawata K, Kochi M, Iwamoto T, Ikeda H, Shien T, Doihara H. Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-19.

Treatment of relapsed refractory multiple myeloma: which new PI-based combination treatments do patients prefer?

Background and objectivesThis study describes preferences of German relapsed refractory multiple myeloma (RRMM) patients with novel proteasome inhibitor-based combination treatments.MethodsPatients with a minimum age of 18 years and a diagnosis of RRMM were included. Their preferences were assessed using a discrete choice experiment design, which was developed based on a literature review and two patient focus group discussions. The final discrete choice experiment design consisted of four attributes, namely “therapy application regimen,” “time without progression of disease,” “possibility of grade ≥3 adverse events (AEs) affecting the blood,” and “possibility of grade ≥3 AE heart failure.”ResultsAnalysis was based on 84 patients (36.9% females, mean age 62.7 years, mean multiple myeloma disease duration 5.5 years). Among the tested attributes, “therapy application regimen” was assigned the highest importance for treatment decisions (38.8%), the second important attribute was “time without progression of disease” (38.7%), followed by “possibility of AE heart failure” (13.9%) and “possibility of AEs affecting the blood” (8.6%). Patients preferred oral intake once a day and once a week over other application modes such as oral intake once a day and once a week plus twice-weekly infusions. Furthermore, they preferred longer disease progression-free time and lower risk of grade ≥3 AEs. The highest overall utility was derived for ixazomib + lenalidomide + dexamethasone (utility: 3.218), compared with lenalidomide + dexamethasone (2.769), and carfilzomib + lenalidomide + dexamethasone (1.928).ConclusionRRMM patients prefer treatments with an all-oral application, a longer disease-progression-free time, and a lower probability of AEs. If patients face tradeoffs, they accept a lower progression-free time and/or higher AE rates to get an all-oral therapy.

P3.08-15 Lung Squamous Cell Carcinoma with Solitary Ocular Metastasis，Successful Treatment: An Interesting and Rare Case Report

The incidence of ocular metastases from lung cancer is reported to be 0.1%-7% according to the international literature. Adenocarcinoma and small-cell lung cancer occupied the most proportion. Lung squamous cell carcinoma with solitary symptomatic ocular metastasis as the initial manifestation who accepted the multidisciplinary team (MDT) treatment has never been reported. In the diagnosis of intracranial disease, ophthalmofundoscopy can be used for follow-up observation and evaluation of therapeutic effects. Whole body PET -CT imaging can be used to identify the primary cancer and determine the disease staging. A 62-year-old woman presented to ophthalmology of hospital with a 1-week history of left eye pain, blurred vision. The ophthalmologist performed ophthalmofundoscopy and optical coherence tomography on the patient(Fig.1A). The ophthalmologist initial diagnosis is metastatic carcinoma to the eye. The diagnostic work was completed with PET-CT which confirmed the central lung cancer in the lower lobe of the right lung with ocular metastasis. After multiple disciplinary team consultations, including surgery, internal medicine, ophthalmology, radiotherapy and imaging department, the patient underwent the right lower lobe resection and lymph node dissection in December 2016. Postoperative pathology diagnose the right lung-squamous-cell carcinoma staged T2aN1. In February 2017, the patient reviewed the eye examination and indicated that the ocular lesions were enlarged. The patient received 4 courses of gemcitabine plus cisplatin regimen chemotherapy. The eye symptoms disappeared completely after 4 courses (Fig.2B). The progression-free time was 11.9 months. There're 16.5 months for the patients has been followed up (March, 2018) from surgery, and the lesion of ocular was still controlled very well without any specific ocular treatment. It's the first report of a rare case with solitary ocular metastasis as the initial manifestation of lung squamous cell carcinoma. The successful treatment of this case was reported to provide a new therapeutic reference for clinicians to encounter similar cases in the future.

Survival outcomes and prognostic factors of patients with intramedullary Grade II ependymomas after surgical treatments

This study evaluated survival outcomes of patients with intramedullary Grade II ependymomas and identify prognostic factors. Electronic searches of PubMed, EMBASE, OVID, the Cochrane Central Register of Controlled Trials were performed to identify trials according to the Cochrane Collaboration guidelines. The objects were intramedullary Grade II ependymoma according to 2007 WHO classification. Kaplan–Meier survival analysis with log-rank test was used to analyze progressive free survival (PFS) and overall survival (OS). Cox proportional hazard model was utilized for multivariate analysis with hazard ratio (HR) and 95% confidence interval (CI) calculated. P values <0.05 were considered statistically significant. A total of 28 studies including 138 cases of intramedullary Grade II ependymomas were retrieved. Patients who were classified as cellular ependymomas or papillary ependymomas had higher risks of progression than those who possessed typical Grade II ependymomas. Patients who were treated with adjuvant therapy had a higher risk of progression than those without adjuvant therapy. OS of patients with giant cell ependymoma was significantly shorter than those with typical Grade II ependymoma. Patients who had cellular or papillary subtype, adjuvant therapy would have a shorter estimated value of progression-free time and a higher risk of progression than typical Grade II ependymomas. Giant cell ependymoma patients would have a higher risk of fatality than those with typical Grade II ependymomas. Definite pathology type and appropriate treatments were foundations of intramedullary Grade II ependymomas’ managements.

Prognostic value of platelet count and lymphocyte to monocyte ratio combination in stage IV non-small cell lung cancer with malignant pleural effusion.

IntroductionA combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet.ObjectivesIn this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment.MethodsBetween January 2012 and July 2016, 217 patients with stage IV NSCLC and MPE undergoing active anticancer treatment were selected for evaluation. If patients had both low LMR (< 2.47) and increased platelet (> 30.0 ×104 mm-3), they were assigned to COP-LMR group 2. Patients with one parameter were assigned to COP-LMR group 1. If none, patients were assigned to COP-LMR group 0.ResultsMedian overall survival (OS) (P < 0.001), progression free survival (PFS) (P < 0.001) and histological feature (P = 0.003) showed significant differences among COP-LMR groups. For COP-LMR groups 0, 1 and 2, median survival times were 35.9, 14.7 and 7.4 months, respectively, while median progression free times were 19.2, 13.3 and 7.4 months, respectively. Older age, male, low albumin, high CRP and high COP-LMR (0 vs 1, P = 0.021, hazard ratio (HR): 1.822, 95% confidence interval (CI): 1.096–3.027 and 0 vs 2, P = 0.003, HR: 2.464, 95% CI: 1.373–4.421) were independent predictive factors for shorter OS. Age, sex, histology, albumin, or CRP had no significant influence on PFS. High COP-LMR was the significant factor in predicting shorter PFS (0 vs 1, P = 0.116 and 0 vs 2, P = 0.007, HR: 1.902, 95% CI: 1.194–3.028).ConclusionsA combination of pretreatment LMR and platelet levels can be used to predict short survival in stage IV NSCLC patients who underwent active anticancer treatment.